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Identification
- Generic Name
- Varespladib methyl
- DrugBank Accession Number
- DB05737
- Background
Varespladib methyl has been investigated for the treatment of Acute Coronary Syndrome. Studies showed that Varespladib methyl treatment resulted in significant positive changes on lipoproteins and inflammation.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Varespladib methyl (DB05737)
- Weight
- Average: 394.427
Monoisotopic: 394.152871816 - Chemical Formula
- C22H22N2O5
- Synonyms
- Varespladib methyl
- Varespladib methyl ester
- External IDs
- A-002
- LY-333013
- LY333013
- S-3013
Pharmacology
- Indication
Investigated for use/treatment in atherosclerosis and coronary artery disease.
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Not Available
- Mechanism of action
A–002 is an orally administered‚ potent inhibitor of secretory phospholipase spla2(spla2)‚ including groups IIA‚ V‚ and X. Atherosclerosis is a disease of the arteries that results from inflammation and the build-up of plaque under the lining of the blood vessel. This build-up can cause vascular swelling and eventual rupture. spla2 levels have been shown to be elevated in patients with both stable and unstable coronary artery disease. Higher levels of the enzyme have been shown to predict an increased risk for future cardiovascular events such as heart attacks and stroke.
Target Actions Organism UPhospholipase A2, membrane associated Not Available Humans UGroup 10 secretory phospholipase A2 Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
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- Varespladib
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenoxyacetic acid derivatives. These are compounds containing an anisole where the methane group is linked to an acetic acid or a derivative.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenoxyacetic acid derivatives
- Direct Parent
- Phenoxyacetic acid derivatives
- Alternative Parents
- N-alkylindoles / Indoles / Phenol ethers / Aryl ketones / Alkyl aryl ethers / Substituted pyrroles / Vinylogous amides / Methyl esters / Heteroaromatic compounds / Primary carboxylic acid amides show 5 more
- Substituents
- Alkyl aryl ether / Aromatic heteropolycyclic compound / Aryl ketone / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Carboxylic acid ester / Ether / Heteroaromatic compound show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0NB98NBX3D
- CAS number
- 172733-08-3
- InChI Key
- VJYDOJXJUCJUHL-UHFFFAOYSA-N
- InChI
- InChI=1S/C22H22N2O5/c1-3-15-20(21(26)22(23)27)19-16(24(15)12-14-8-5-4-6-9-14)10-7-11-17(19)29-13-18(25)28-2/h4-11H,3,12-13H2,1-2H3,(H2,23,27)
- IUPAC Name
- methyl 2-{[1-benzyl-3-(carbamoylcarbonyl)-2-ethyl-1H-indol-4-yl]oxy}acetate
- SMILES
- CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)C=CC=C2N1CC1=CC=CC=C1
References
- General References
- Not Available
- External Links
- PubChem Compound
- 9886917
- PubChem Substance
- 347827740
- ChemSpider
- 8062590
- ChEMBL
- CHEMBL2105659
- ZINC
- ZINC000001550156
- Wikipedia
- Varespladib_methyl
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Terminated Treatment Acute Coronary Syndrome (ACS) 1 somestatus stop reason just information to hide 2 Completed Prevention Coronary Artery Disease (CAD) 3 somestatus stop reason just information to hide 2 Completed Treatment Acute Coronary Syndrome (ACS) 1 somestatus stop reason just information to hide 2 Completed Treatment Envenoming / Envenoming, Snake / Snake Bite / Snake Envenomation 1 somestatus stop reason just information to hide 2 Recruiting Treatment Envenoming, Snake / Snake Bite 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00343 mg/mL ALOGPS logP 3.34 ALOGPS logP 2.92 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 13.81 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 100.62 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 107.66 m3·mol-1 Chemaxon Polarizability 41.16 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0ab9-0009000000-b888ea2a35cd45722691 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00or-0097000000-5874401b5e2315b473cd Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004l-3019000000-205416385926fd98c4ca Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-014l-2059000000-32c13993148c09a6a849 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-6091000000-7751cb93ecafee4e1417 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004l-0090000000-a4853f45c747eea42d50 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 188.05835 predictedDeepCCS 1.0 (2019) [M+H]+ 190.41634 predictedDeepCCS 1.0 (2019) [M+Na]+ 197.08113 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:10455175, PubMed:10681567, PubMed:2925633). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10455175, PubMed:10681567). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:10358193, PubMed:11694541). Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response (PubMed:25082876). Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (PubMed:14998370). Independent of its catalytic activity, acts as a ligand for integrins (PubMed:18635536, PubMed:25398877). Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 (PubMed:18635536, PubMed:25398877). Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:25398877). Induces cell proliferation in an integrin-dependent manner (PubMed:18635536)
- Specific Function
- Calcium ion binding
- Gene Name
- PLA2G2A
- Uniprot ID
- P14555
- Uniprot Name
- Phospholipase A2, membrane associated
- Molecular Weight
- 16082.525 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids (PubMed:12021277, PubMed:9188469). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with preference for phosphatidylcholines and phosphatidylglycerols over phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty acyls (PubMed:12021277, PubMed:12359733). Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (PubMed:12021277). Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (PubMed:12021277). Efficiently hydrolyzes and inactivates platelet activating factor (PAF), a potent lipid mediator present in oxidized LDL (PubMed:16962371). May act in an autocrine and paracrine manner. Secreted by lung epithelium, targets membrane phospholipids of infiltrating eosinophils, releasing arachidonate and boosting eicosanoid and cysteinyl leukotriene synthesis involved in airway inflammatory response (By similarity). Secreted by gut epithelium, hydrolyzes dietary and biliary phosphatidylcholines in the gastrointestinal lumen (By similarity). Plays a stem cell regulator role in colon epithelium. Within intracellular compartment, mediates Paneth-like cell differentiation and its stem cell supporting functions by inhibiting the Wnt signaling pathway in intestinal stem cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ISCs and tissue regeneration (By similarity). May participate in hair follicle morphogenesis by regulating phosphatidylethanolamines metabolism at the outermost epithelial layer and facilitating melanin synthesis (By similarity). By releasing lysophosphatidylcholines (LPCs) at sperm acrosome, controls sperm cell capacitation, acrosome reaction and overall fertility (By similarity). May promote neurite outgrowth in neuron fibers involved in nociception (By similarity). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria (PubMed:12359733). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541). In pulmonary epithelium, may contribute to host defense response against adenoviral infection. Prevents adenovirus entry into host cells by hydrolyzing host cell plasma membrane, releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and viral infection. Likely prevents adenoviral entry into the endosomes of host cells (PubMed:16146426). May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells (By similarity)
- Specific Function
- 1-alkyl-2-acetylglycerophosphocholine esterase activity
- Gene Name
- PLA2G10
- Uniprot ID
- O15496
- Uniprot Name
- Group 10 secretory phospholipase A2
- Molecular Weight
- 18153.04 Da
Drug created at November 18, 2007 18:27 / Updated at February 21, 2021 18:51